Microscopy Core Facility Visualization of tissues, cells, viruses and molecules by microscopy is essential for probing concepts and creating new avenues of cancer research. Techniques have evolved over the past decade that have expanded the utility of both light and electron microscopy to interrogate cells at all levels. The UNC LCCC Microscopy Core has continued to evolve over the last cycle upgrading instrumentation in its highly utilized Light Microscopy component and in its Electron Microscopy component, as well as adding major instrumentation in intravital microscopy. Substantial utilization of the first component and more specialized use of electron microscopy have resulted in an outstanding publication record. This combined core offers LCCC members access to state-of-the art service in light microscopy together with research-based ElVI and intravital imaging. While the core grant provides only a small fraction of the total operational costs, this key contribution makes it possible to provide access to the instruments, training, and staff at little to no cost to LCCC members. As a result, the core has had a major impact on the cancer-related research of the LCCC. Multiple publications from the core over the past six years include papers in Cell, PNAS and Nature. New instrumentation obtained by the Core represented an investment of nearly $3,000,000 including significant upgrades for cryoEM to for the EM core, new CLSM and wide field instruments for the light microscopy facility, and a multiphoton microscope for intravital work. Over 60 LCCC members in eight programs used the Core during 2009. One highlight of the light microscopy core over the coming five years will be the addition of bio-sensor imaging methods in collaboration with Dr Klaus Hahn to probe key signaling pathways and to advance multi-spectral confocal imaging involving five or more colored indicators. The EM core will be bringing new cryoEM methods to the LCCC faculty and the intravital capability will allow investigators to study tumor and stromal cells inside of live animals. The Microscopy Core requests $212,590 in CCSG representing 39% of operating costs for 2010. Last year 87% of the core usage was by center members. A significant increase in the budget is proposed to make available expansion of existing services and access to a number of new microscopes and techniques added in the past two years.